Diverse functions of WD40 repeat proteins in histone recognition: Figure 1.

Abstract

WD40 repeat proteins have been shown to bind the histone H3 tail at the center of their ␤-propeller structure. In contrast, in this issue of Genes & Development, Song and colleagues (pp. 1313-1318) demonstrate that the WD40 repeat protein p55 binds a structured region of H4 through a novel binding pocket on the side of ␤-propeller, illustrating a diversity of histone recognition by WD40 repeat proteins.The association of WD40 repeat proteins with histones and nucleosomes is of increasing interest because of their functions in a variety of histone/chromatin-modifying complexes. In this issue of Genes & Development, Song et al. (2008) solve the crystal structure of p55, a Drosophila seven-WD40-repeat protein. Binding of p55 is shown to be incompatible with the histone fold of H4 and results in a change in H4 structure. The interaction of p55 with H4 is distinct from that of previously characterized WD40 repeat proteins and utilizes a novel binding pocket on the side of the ␤-propeller instead of the center of the propeller. This novel p55-H4 interaction extends the known contacts by which WD40 repeat proteins recognize histones and reveals diversity in the manner in which this important recognition domain functions. WD40 repeat proteins are important for a variety of cellular functionsWD40 repeats were first noted in the ␤-subunit of the heterotrimeric GTP-binding protein (G protein) (Fong et al. 1986). The G protein structure contained seven WD40 repeats. Each repeating unit formed one of seven ␤-propeller blades with four small anti-parallel ␤-sheets built into a toroidal structure with a tapered end and central canal (Wall et al. 1995;Neer and Smith 2000). The conserved core of repeating units contained 44-60 residues that ended with tryptophan (W) and aspartate (D). Since the initial identification of the WD40 repeats, >160 WD40 repeat proteins have been identified, with the majority found in higher eukaryotes (Smith et al. 1999). Each family member has between four and 10 copies of the WD40 repeats. In general, WD40 repeat proteins have been associated with a diverse range of cellular processes, including RNA processing, transcriptional regulation (Williams et al. 1991;Hoey et al. 1993), mitotic spindle formation (de Hostos et al. 1991;Vaisman et al. 1995), regulation of vesicle formation and vesicular trafficking (Pryer et al. 1993), and control of cell division (Feldman et al. 1997).Four WD40 repeat proteins-WDR5, RbBP5, RbAp48/ 46 (each with seven repeats)-and the Drosophila homolog of RbAp48/46, p55, are components of histone-modifying complexes (Fig. 1). WDR5 is associated with SET domain-containing methyltransferases, such as Set1, MLL, MLL2, and MLL3/4 (Wysocka et al. 2005;Dou et al. 2006;Mendjan et al. 2006;Cho et al. 2007). In addition to its role in histone methylation, WDR5 and WDS, the Drosophila homolog of WDR5, are associated with several histone acetyltransferase (HAT) complexes, including the MSL (male-specific lethal) complex (Mendjan et al. 2006); the ATAC (Ada Two A-containing) complex, whi...

The Drosophila wings apart Gene Anchors a Novel, Evolutionarily Conserved Pathway of Neuromuscular Development

“…These repeats form propeller-like structures, termed b-propellers, created by the folding of four antiparallel b-sheets (reviewed in Holm et al 2001). This protein family is known to have roles in signal transduction, messenger RNA processing, gene regulation, vesicular trafficking, and regulation of the cell cycle (reviewed in Skurat andDietrich 2004 andin Suganuma et al 2008). These findings are consistent with the premise that genes whose mutants have pleiotropic effects can be members of broadly used biological pathways.…”

“…Orthologs include the TTG1 gene that regulates root, shoot, and leaf patterning in Arabidopsis (Walker et al 1999) and vertebrate craniofacial and muscle patterning genes (Nissen et al 2006). WD40 repeat proteins mediate protein-protein interactions and contain 4-10 repeating units of 44-60 residues ending in tryptophan and aspartate (WD) (reviewed in Holm et al 2001 andSuganuma et al 2008). These repeats form propeller-like structures, termed b-propellers, created by the folding of four antiparallel b-sheets (reviewed in Holm et al 2001).…”

The WD40-Repeat Proteins NFC101 and NFC102 Regulate Different Aspects of Maize Development through Chromatin Modification

“…The involvement of nfc101/nfc102 in regulating different pathways, including TE transcription, G1/S cell cycle transition, and DNA repair, is supported by several lines of evidence from present and past studies Varotto et al, 2003;Casati et al, 2008;Campi et al, 2012). It is worth noting that all plant and mammalian MSI family members characterized to date are involved in multiple regulatory pathways, with the common theme that they are usually associated with chromatin modification and remodeling (Hennig et al, 2005;Suganuma et al, 2008). Altogether, these observations suggest that NFC101/NFC102 are components of distinct chromatin modifying complexes (i.e., HDAC dependent or independent), operating in different biological processes, and that the major role of these WDrepeat proteins is to facilitate and stabilize interactions between other complex components by means of their peculiar b-propeller architecture.…”

“…The MSI1-like proteins are a particular class of WD40-repeat proteins, named for the founding member isolated in a screen for multicopy suppressors of the ira1 mutation in budding yeast (Saccharomyces cerevisiae; Ruggieri et al, 1989). This class contains mammalian retinoblastoma-associated proteins RbAp46/ 48 and their Drosophila melanogaster homolog p55, which are components of complexes involved in chromatin assembly and modification (Suganuma et al, 2008).…”

Role of non-motile microtubule-associated proteins in virus trafficking

“…Finally, WD40-repeats proteins are characterized by the presence of repeating units of 44-60 variable residues that end with tryptophan (W) and aspartate (D) dipeptides (54). In the last decade, multiple WD40 protein complexes have been identified, which generally function as rigid platforms for protein-protein and protein-DNA interactions and are involved in diverse range of cellular processes, such as signal transduction, gene transcriptional regulation, protein modifications, cytoskeleton assembly, vesicular trafficking, DNA damage and repair, cell death and control of cell division (55).…”